1. Field of the Invention
The present invention relates to a pharmaceutical dosage form which contains diphenhydramine and/or a pharmaceutically acceptable salt thereof in combination with at least one additional active ingredient. The dosage form releases diphenhydramine and the additional active ingredient at rates which provide pharmaceutically suitable plasma concentrations of both components over similar periods of time. The present invention also relates to a process for manufacturing the dosage form and to methods for alleviating conditions which can be alleviated by diphenhydramine and the at least one additional active ingredient.
2. Discussion of Background Information
Diphenhydramine is a histamine antagonist that possesses antihistaminic, antitussive, sedative, antimotion-sickness, antiemetic, and anticholinergic effects. It is used, for example, for the amelioration of allergic reactions, to reduce excessive coughing, for the treatment of motion sickness and the prevention and control of nausea and vomiting associated with certain types of anesthesia and surgery. Allergic reactions, in particular, which can be treated or ameliorated with diphenhydramine are often accompanied by conditions which cannot satisfactorily be ameliorated or treated with diphenhydramine, but may be treated or ameliorated by other drugs, e.g., expectorants, mucus thinning drugs, decongestants, (morphine derived) antitussives, and/or analgesics. A single dose of diphenydramine can provide a therapeutically effective plasma concentration for about 4 to 6 hours, whereas a single dose of other drugs will often provide a therapeutically effective plasma concentration for a considerably shorter or longer period. For example, a single dose of an expectorant such as guaifenesin will usually provide relief for only about one hour, and decongestants, and analgesics usually provide relief for about 3 to 8 hours per single dose. Codeine phosphate will usually provide relief for 2.9±0.7 hours. With a corresponding combination, the diphenhydramine would provide the desired therapeutic effect when the other drug has ceased to be effective or would cease to be effective while the other drug retained its therapeutic effects.
It would be desirable if patients suffering from, e.g., respiratory congestion, inflammation of the respiratory mucosa and sinus cavities, weeping eyes, rhinorrhea, eustachian tube congestion, cough, nausea, aching joints, headache and fever and related symptoms, for which diphenhydramine is indicated, would also obtain relief, over a similar time period, from one or more conditions for which drugs different from diphenhydramine are indicated, by the administration of a single dose of a dosage form such as, e.g., a tablet, liquid, syrup, suspension, capsule or gel and the like which provides both diphenhydramine and one or more other drugs. It would also be desirable to have available a dosage form which provides, in a single dose, diphenhydramine (together with or without any additional drug) over different time periods and/or at different rates, for example, in order to make diphenhydramine available as fast as possible and to also provide diphenhydramine over an extended period of time so as to maintain a therapeutic plasma concentration of diphenhydramine for as long as desired and/or possible.